2,2-Dimethylmorpholine → 2,2-Dimethyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine

HRID 1431384Notes

Reaction equation

HRID 1431384 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:17][C:18]1([CH3:24])[O:23][CH2:22][CH2:21][NH:20][CH2:19]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(C)C=CC=CC=1>[CH3:17][C:18]1([CH3:24])[O:23][CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=2)[CH2:19]1

Participants

7

Reactant 4

HCID 189596742,2-DimethylmorpholineHCID 23676156Sodium t-butoxideHCID 596312064-(5-Chloro-3-nitropyridin-2-yl)morpholineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 596311902,2-Dimethyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (850 mg, 3.49 mmol; described herein), 2,2-dimethylmorpholine (480 μL, 4180 μmol), tris(dibenzylideneacetone)dipalladium(o) (224 mg, 0.244 mmol), 2-(dicyclohexylphosphino)-2,4,6,-tri-i-propyl-1,1-biphenyl (249 mg, 0.523 mmol), sodium 2-methylpropan-2-olate (671 mg, 6.98 mmol), and toluene (517 mL) was refluxed overnight, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with satd aq. sodium bicarbonate and brine, then the organic layer dried (magnesium sulfate) and concentrated. Column chromatography afforded 2,2-dimethyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine as a red solid. Mass Spectrum (ESI) m/e=323.2 (M+1).

Workup

  1. temperaturewas refluxed overnight
  2. concentrationconcentrated
  3. washwashed with satd aq. sodium bicarbonate and brine
  4. dry with materialthe organic layer dried (magnesium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c28460f047664701b304d247e5cef496
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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